Fig. 3. Extensive coevolution in DNA replication genes.

(A) Cartoon representation of DNA replication. Exemplary complex specific subnetworks are depicted in (B) to (D). (B) Extensive coevolution between orthologous genes that encode the helicase, minichromosome maintenance (MCM) complex, which functions as a helicase. (C) Coevolution in the orthologous genes that encode the DNA polymerase α-primase complex and (D) DNA polymerase ε complex, which are responsible for RNA primer synthesis and leading strand DNA synthesis, respectively. Edges in blue connect orthologous genes that are significantly coevolving. Orthologous genes and complexes in bold have signatures of coevolution. Orthologous genes and complexes are colored according to orthologous gene community assignment. Complexes, such as the DNA polymerase α-primase complex, are depicted in multiple colors reflecting the multiple orthologous gene communities represented within the complex. There is significant coevolution across all DNA replication orthologous genes (P < 0.001; permutation test) as well as the multimeric complexes such as the MCM complex (P < 0.001 for each pathway; permutation test).